Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617000645358
Ethics application status
Approved
Date submitted
18/04/2017
Date registered
4/05/2017
Date last updated
4/05/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Combination therapy with mandibular advancement splint and continuous positive airway pressure (CPAP) for sub-optimally treated obstructive sleep apnoea
Scientific title
Can mandibular advancement improve CPAP effectiveness in patients sub-optimally treated with CPAP using an oronasal mask?
Secondary ID [1] 291716 0
Nil
Universal Trial Number (UTN)
Nil
Trial acronym
Nil
Linked study record
Nil

Health condition
Health condition(s) or problem(s) studied:
Obstructive sleep apnoea 302896 0
Condition category
Condition code
Respiratory 302384 302384 0 0
Sleep apnoea

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will use CPAP in autoset mode (APAP) during sleep on all nights for a period of 4 weeks (own control group). During this period, APAP will be administered via the participants usual oronasal mask (ie full face mask) with a pressure range of 5-20cm of water. Participants with be then fitted with an O2Vent T Mandibular Advancement Device via a trained prosthodontist Dr Chris Hart. The O2Vent T is a customized duo-block titratable oral appliance that is registered with the Therapeutic Goods Administration (TGA) as a Class I therapeutic product. Fitting and further advancement of the device will occur over 1 to 3 sessions total depending on the individual participants response and overall positioning of the device. Participants will use the O2Vent T Mandibular Advancement Splint in combination with their APAP for a 4-12 week period depending on the necessary number of advancements made (ie 0 advancements = 4 weeks; 1 advancements = 8 weeks; 2 advancements = 12 weeks). The decision for further advancement will depend on the dental reviews mentioned above. Data will be gathered for each treatment period (ie 4 week control group and 4-12 week treatment group). For the 4-12 weak treatment period, the data gathered will be obtained across each separate 4 week period (within the 4-12 weeks) pending the number of advancements made during dental reviews. Data attained will include daily and total usage, required APAP pressures, AHI and leak. All of this complete data will be accessible and attained via the participants APAP machine downloads for all treatment periods described. There is deemed to be no significant washout period in between the two treatments, however, if this does occur, patients will simply continue on their usual CPAP for that time. This will not impact on the study results.
Intervention code [1] 297801 0
Treatment: Devices
Comparator / control treatment
As above, participants will act as their own controls (ie monotherapy with APAP).
Control group
Active

Outcomes
Primary outcome [1] 301788 0
Apnoea/hypopnoea index (AHI). This will be downloaded from the participants APAP machine data attained during their relevant treatment period (ie APAP monotherapy period and then combination therapy period)
Timepoint [1] 301788 0
The AHI will be downloaded at the end of each of the relevant treatment periods (ie 4 week APAP monotherapy period and the 4-12 week combination therapy period). The average AHI overall for each treatment period will be obtained via the APAP machine downloads (this will be for each entire treatment period).
Primary outcome [2] 301789 0
CPAP pressure requirement. This will be downloaded from the participants APAP machine data attained during their treatment period (ie APAP monotherapy period and then combination therapy period).
Timepoint [2] 301789 0
The CPAP pressure requirement will be downloaded at the end of each of the relevant treatment periods (ie 4 week APAP monotherapy period and the 4-12 week combination therapy period). The CPAP pressure requirement for each treatment period will be obtained via the APAP machine downloads (this will be for each entire treatment period).
Secondary outcome [1] 333875 0
Symptoms - defined by ESS (Epworth Sleepiness Score)
Timepoint [1] 333875 0
The ESS questionnaire will be filled out by Participants at the beginning of the study, at the end of the APAP monotherapy period, and again at the end of the combination therapy period.
Secondary outcome [2] 333876 0
Compliance / Usage. This will simply be downloaded from the participants APAP machine data attained during their treatment period (ie APAP monotherapy period and then combination therapy period)
Timepoint [2] 333876 0
Data demonstrating compliance / usage will be downloaded at the end of each of the relevant treatment periods (ie 4 week APAP monotherapy period and the 4-12 week combination therapy period). The average daily and overall usage for each treatment period will be obtained via the APAP machine downloads (this will be for each entire treatment period).
Secondary outcome [3] 333877 0
Leak. This refers to the average amount of leak in litres/minute and will be downloaded from the participants APAP machine data obtained during their entire treatment period (ie APAP monotherapy period and then combination therapy period).
Timepoint [3] 333877 0
Data demonstrating average leak will be downloaded at the end of each of the relevant treatment periods (ie 4 week APAP monotherapy period and the 4-12 week combination therapy period). The average overall leak (not number of leaks) for each treatment period will be obtained directly via the APAP machine downloads (this will be for each entire treatment period).
Secondary outcome [4] 334178 0
FOSQ (Functional Outcomes of Sleep Questionnaire).
Timepoint [4] 334178 0
The FOSQ questionnaire will be filled out by Participants at the beginning of the study, at the end of the APAP monotherapy period, and again at the end of the combination therapy period.

Eligibility
Key inclusion criteria
Participants will be selected based on the following inclusion criteria:
1. Obstructive sleep apnoea as diagnosed by polysomnography with AHI>5
2. Current treatment with CPAP using an oronasal mask deemed as suboptimal
3. Assessed as dentally suitable for oral appliance
4. Able to provide written informed consent to all study procedures, investigators to access clinical records from treating physician and agrees to adhere to all protocol requirements
5. Geographically suitable
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Pregnant or lactating females
2. Participating in another interventional clinical trial
3. Uncontrolled or untreated cardiovascular disease
4. Central sleep apnoea events (>5/hr)
5. Previous uvulopalatopharyngoplasty (UPPP)
6. Severe somatic or psychiatric disorders
7. Periodontal disease, temporomandibular

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
NA
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
NA
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Prospective case-control crossover study to determine whether treatment effectiveness can be improved with combination CPAP and MAD in a group of patients with OSA who are sub-optimally treated with CPAP using an oronasal mask.

Participants will be monitored for CPAP efficacy and compliance using their usual oronasal mask for 4 weeks whilst using an auto-titrating CPAP (APAP). They will then be fitted with a customized MAD (O2Vent T) and use this in combination with APAP with oronasal mask. Combination therapy will again occur over a 4 week period, although further advancement of the MAD may need occur up to 2 times if clinically indicated. If this occurs, the combination therapy period may be extended to up to 12 weeks maximum.

Effectiveness of both treatment will be compared using downloaded data from each participants APAP machines at the end of the relevant treatment periods (ie 4 weeks for the APAP monotherapy period and 4-12 weeks for the combination therapy period).

Whilst this is a prospective case series, previous CPAP downloads and sleep study results will be used to evaluate current treatment effect and assess the meeting of inclusion criteria as sub-optimally treated with CPAP. Data from previous sleep studies and downloads may also be collected as part of this research.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
The primary outcome will be to compare CPAP pressures required with and without MAD.
Prior data indicate that the difference in the response of matched pairs is normally distributed with standard deviation. If the true difference in the mean response of matched pairs is 2, we will need to study 16 pairs of subjects to be able to reject the null hypothesis that this response difference is zero with probability (power) 0.9. The Type I error probability associated with this test of this null hypothesis is 0.05.

Whilst this study is not powered to detect differences in compliance, compliance with and without MAD will be tested for significance using paired t-tests.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
15/05/2017
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
16
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 7859 0
Greenslopes Private Hospital - Greenslopes
Recruitment postcode(s) [1] 15802 0
4120 - Greenslopes

Funding & Sponsors
Funding source category [1] 296216 0
Commercial sector/Industry
Name [1] 296216 0
Oventus Medical Limited
Country [1] 296216 0
Australia
Primary sponsor type
Hospital
Name
Sleep Care - Greenslopes Private Hospital
Address
Sleep Care, Sleep Investigation Unit
Greenslopes Private Hospital
Newdegate Street
Greenslopes, QLD 4120
Country
Australia
Secondary sponsor category [1] 295127 0
Commercial sector/Industry
Name [1] 295127 0
Oventus Medical Limited
Address [1] 295127 0
1 Swann Road, Indooroopilly
PO Box 190, Indooroopilly, 4068 QLD Australia
Country [1] 295127 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297455 0
Greenslopes Research and Ethics Committee
Ethics committee address [1] 297455 0
Greenslopes Private Hospital
Newdegate Street
Greenslopes, QLD, 4102
Ethics committee country [1] 297455 0
Australia
Date submitted for ethics approval [1] 297455 0
30/11/2016
Approval date [1] 297455 0
20/12/2016
Ethics approval number [1] 297455 0
Protocol 16/71

Summary
Brief summary
Obstructive sleep apnoea (OSA) is common and an important contributor to cardiovascular disease, stroke, and depression. The first line treatment for OSA is continuous positive airway pressure (CPAP) which is highly effective in treating OSA. However, up to 50% of patients are unable or unwilling to tolerate CPAP. Nasal masks are most frequently used, however oronasal masks covering the nose and mouth, may be chosen due to patient preference, nasal obstruction or air leak through the mouth. There is growing evidence suggesting that oronasal masks are less effective in controlling OSA. Patients using oronasal masks are a clinically difficult group of patients to treat, often requiring higher CPAP pressures, with significant mask leaks, a higher residual AHI and lower adherence to treatment.

Mandibular Advancement Devices (MAD) are emerging as an alternative treatment particularly in patients with mild to moderate OSA, CPAP intolerant OSA and primary snorers. The O2Vent T is a custom-made MAD with an enclosed airway that allows airflow through the device. Like all MADs, the lower jaw is brought forward to stabilize the upper airway, however unlike other devices, patients can also breathe through the device while the jaw position stabilized. This may be of benefit to those with nasal obstruction and a tendency to mouth breathe i.e. patients using oronasal masks.

Our aim is to assess whether treatment effectiveness can be improved with combination CPAP and MAD, in a group of patients with OSA who are sub-optimally treated with CPAP using an oronasal mask. Treatment effectiveness is a clinical decision based on factors including compliance, residual Apnoea-Hypopnea Index (AHI), pressure requirements and leak. We hypothesize that compared to CPAP with oronasal mask, combination therapy will result in:
a) Lower pressure requirements
b) Lower AHI
c) Lower leak
d) Better compliance

Participants will be monitored for CPAP efficacy and compliance using their oronasal mask for 4 weeks using an auto-titrating CPAP (APAP). They will be fitted with a customized MAD (O2Vent T) and then use this in combination with their APAP (combination therapy) for a further 4 week period. Further advancement of the MAD may need to occur if clinically indicated (ie for a period of 4 to 12 weeks maximum). Treatment effectiveness between the groups will be compared using downloaded data from the participants APAP machines. This will include AHI, pressure requirements, usage and leak, which will all be downloaded from the participants APAP machines at the end of the relevant treatment periods.
Trial website
NA
Trial related presentations / publications
Public notes
Nil
Attachments [1] 1641 1641 0 0
/AnzctrAttachments/372757-Protocol - Combination therapy for OSA V1.0 Final.pdf (Protocol)
Attachments [2] 1642 1642 0 0
/AnzctrAttachments/372757-PICF - Combination therapy for OSA V1.0 Final.pdf (Participant information/consent)
Attachments [3] 1644 1644 0 0
/AnzctrAttachments/372757-Oventus Project - Ethics Approval.pdf (Ethics approval)

Contacts
Principal investigator
Name 74086 0
Dr Robyn O'Sullivan
Address 74086 0
Sleep Care, Sleep Investigation Unit
Suite 3a, Greenslopes Private Hospital
Newdegate Street, Greenslopes, QLD, 4120
Country 74086 0
Australia
Phone 74086 0
+617 33947036
Fax 74086 0
Email 74086 0
[email protected]
Contact person for public queries
Name 74087 0
Dr Timothy Baird
Address 74087 0
Sleep Care, Sleep Investigation Unit
Suite 3a, Greenslopes Private Hospital
Newdegate Street, Greenslopes, QLD, 4120
Country 74087 0
Australia
Phone 74087 0
+617 33947036
Fax 74087 0
Email 74087 0
[email protected]
Contact person for scientific queries
Name 74088 0
Dr Timothy Baird
Address 74088 0
Sleep Care, Sleep Investigation Unit
Suite 3a, Greenslopes Private Hospital
Newdegate Street, Greenslopes, QLD, 4120
Country 74088 0
Australia
Phone 74088 0
+617 33947036
Fax 74088 0
Email 74088 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.